Cutaneous basophil hypersensitivity is a delayed time course immune reaction that has been distinguished from classical tuberculin-type hypersensitivity by the accumulation of large numbers of basophils. In experimental guinea pig model systems involving soluble protein antigens and haptens it has been established that cutaneous basophil reactions are mediated by thymic derived lymphocytes (T cells) or 7S IgG1 antibodies. Basophils arriving at these reactions can be triggered by antigen to release mediators such as histamine. This research proposal submits a comprehensive program to investigate cutaneous basophil hypersensitivity responses that are associated with immune resistance to ectoparasitic ticks. We will study the factors that may enable basophils to mediate this resistance. Experiments will be performed to characterize the sensitized cells and antibodies that may lead to the tissue accumulation and subsequent activation of basophils to mediate resistance. We will determine whether basophils are required to effect immune resistance by depleting basophils with a specific anti-basophil serum, and will study how basophils effect the immune resistance. Experiments will also be conducted to determine how ticks are adversely affected by this response. Finally, we will investigate the genetic and immunological factors mediating innate resistance to ectoparasitic ticks.